The role of the cyclic nucleotides adenosine 3':5' monophosphate (cyclic AMP) and guanosine 3':5' monophosphate (cyclic GMP) in synaptic transmission is under study using cultured cells of neural origin. The topics of interest during the current year have been the following: 1) The alpha-receptor-mediated inhibition of adenylate cyclase activity by norepinephrine in neuroblastoma x glioma hybrid cells; and 2) characterization of a compensatory increase of adenylate cyclase activity in cells treated for 10 hours or longer with norepinephrine and study of the mechanism of this increase, which results in cell tolerance to and dependence upon norepinephrine with respect to cyclic AMP synthesis.